In the current study, a combination of precipitation polymerization and modified sol-gel methods were developed to prepare the novel hyaluronic acid-decorated pH and redox dual-stimuli responsive poly(methacrylic acid)/mesoporous organosilica nanoparticles with a core-shell structure for controlled drug release. The nanocarriers have a proper particle size of <200 nm, high negative zeta potential greater than −30 mV, controllable diameter, and tunable shell thickness. The prepared nanoparticles were able to entrap over 70 % of quercetin with a drug loading of >10 %, due to the mesoporous shell. In vitro drug release profiles indicated that the systems had good stability under normal physiological media, while the cumulative release was significantly accelerated at the simulated tumor tissue condition, which shows pH and redox-dependent drug release. In vitro cell viability and apoptosis assay proved that the obtained nanomaterials possess relatively good biocompatibility, and drug-loaded targeted nanoparticles exhibited greater cytotoxicity on MCF-7 human breast cancer cells than free drug and non-targeted nanocarriers due to the enhanced cellular uptake of nanoparticles via CD44 receptors overexpressed. All these findings demonstrated that proposed nanocarriers might be promising as a smart drug delivery system to improve the antitumor efficacy of chemotherapeutic drugs
